Genomes and Genes
Gene Symbol: Clec7a
Description: C-type lectin domain family 7, member a
Alias: BGR, Clecsf12, beta-GR, C-type lectin domain family 7 member A, C-type (calcium dependent, carbohydrate recognition domain) lectin, superfamily member 12, C-type lectin superfamily member 12, DC-associated C-type lectin 1, beta-glucan receptor, dectin-1, dendritic cell-associated C-type lectin 1
- Rogers N, Slack E, Edwards A, Nolte M, Schulz O, Schweighoffer E, et al. Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity. 2005;22:507-17 pubmed..These results identify a novel signaling pathway involved in pattern recognition by C type lectins and suggest a potential role for Syk kinase in regulation of innate immunity. ..
- Ariizumi K, Shen G, Shikano S, Xu S, Ritter R, Kumamoto T, et al. Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning. J Biol Chem. 2000;275:20157-67 pubmed..Not only do these results document the efficacy of subtractive cDNA cloning for the identification of unique genes expressed by DC, they also provide a framework for studying the physiological function of dectin-1. ..
- Xu S, Huo J, Lee K, Kurosaki T, Lam K. Phospholipase Cgamma2 is critical for Dectin-1-mediated Ca2+ flux and cytokine production in dendritic cells. J Biol Chem. 2009;284:7038-46 pubmed publisher..Thus, our data indicate that pattern recognition receptors such as Dectin-1 could elicit Ca2+ signaling and that PLCgamma2 is a critical player in the Dectin-1 signal transduction pathway. ..
- LeibundGut Landmann S, Osorio F, Brown G, Reis E Sousa C. Stimulation of dendritic cells via the dectin-1/Syk pathway allows priming of cytotoxic T-cell responses. Blood. 2008;112:4971-80 pubmed publisher..These data highlight the ability of non-TLR receptors to bridge innate and adaptive immunity and suggest that dectin-1 agonists may constitute useful adjuvants for immunotherapy and vaccination. ..
- Hara H, Ishihara C, Takeuchi A, Imanishi T, Xue L, Morris S, et al. The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. Nat Immunol. 2007;8:619-29 pubmed..Thus, the activation of lymphoid and myeloid cells through ITAM-associated receptors or Toll-like receptors is regulated by CARMA1-Bcl-10 and CARD9-Bcl-10, respectively. ..
- Huang H, Ostroff G, Lee C, Agarwal S, Ram S, Rice P, et al. Relative contributions of dectin-1 and complement to immune responses to particulate ?-glucans. J Immunol. 2012;189:312-7 pubmed publisher..In addition, Th-skewing after GP-based immunization was altered in C3(-/-) mice. ..
- Goodridge H, Reyes C, Becker C, Katsumoto T, Ma J, Wolf A, et al. Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. Nature. 2011;472:471-5 pubmed publisher..Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) ..
- Willment J, Lin H, Reid D, Taylor P, Williams D, Wong S, et al. Dectin-1 expression and function are enhanced on alternatively activated and GM-CSF-treated macrophages and are negatively regulated by IL-10, dexamethasone, and lipopolysaccharide. J Immunol. 2003;171:4569-73 pubmed..These results correlate with the known effects of these cytokines and other agents on the ability of the immune system to recognize and respond to fungal pathogens. ..
- Robinson M, Osorio F, Rosas M, Freitas R, Schweighoffer E, Gross O, et al. Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. J Exp Med. 2009;206:2037-51 pubmed publisher..Thus, Dectin-2 constitutes a major fungal PRR that can couple to the Syk-CARD9 innate signaling pathway to activate DCs and regulate adaptive immune responses to fungal infection. ..
- Dennehy K, Willment J, Williams D, Brown G. Reciprocal regulation of IL-23 and IL-12 following co-activation of Dectin-1 and TLR signaling pathways. Eur J Immunol. 2009;39:1379-86 pubmed publisher..Furthermore, these data reveal how the collaboration of different PRR can tailor specific responses to infectious agents. ..
- Taylor P, Brown G, Herre J, Williams D, Willment J, Gordon S. The role of SIGNR1 and the beta-glucan receptor (dectin-1) in the nonopsonic recognition of yeast by specific macrophages. J Immunol. 2004;172:1157-62 pubmed..These studies have identified SIGNR1 as a major MR for fungal and other pathogens present on specific subsets of Mphi. ..
- Heinsbroek S, Taylor P, Rosas M, Willment J, Williams D, Gordon S, et al. Expression of functionally different dectin-1 isoforms by murine macrophages. J Immunol. 2006;176:5513-8 pubmed..These results are the first evidence that dectin-1 isoforms are functionally distinct and indicate that differential isoform usage may represent a mechanism of regulating cellular responses to beta-glucans. ..
- LeibundGut Landmann S, Gross O, Robinson M, Osorio F, Slack E, Tsoni S, et al. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol. 2007;8:630-8 pubmed..Our data indicate that signaling through Syk and CARD9 can couple innate to adaptive immunity independently of Toll-like receptor signals and that CARD9 is required for the development of T(H)-17 responses to some pathogens. ..
- Carvalho A, Giovannini G, De Luca A, D Angelo C, Casagrande A, Iannitti R, et al. Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis. Cell Mol Immunol. 2012;9:276-86 pubmed publisher..Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling. ..
- Brown G, Herre J, Williams D, Willment J, Marshall A, Gordon S. Dectin-1 mediates the biological effects of beta-glucans. J Exp Med. 2003;197:1119-24 pubmed..Furthermore, these studies implicate Dectin-1 in the production of TNF-alpha in response to fungi, a critical step required for the successful control of these pathogens. ..
- Viriyakosol S, Fierer J, Brown G, Kirkland T. Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on Toll-like receptor 2 and Dectin-1. Infect Immun. 2005;73:1553-60 pubmed..Taken together, these results show that cytokine responses in mouse peritoneal macrophages to C. posadasii spherules are dependent on TLR2, MyD88, and Dectin-1...
- Underhill D, Rossnagle E, Lowell C, Simmons R. Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood. 2005;106:2543-50 pubmed..The proportion of macrophages using this signaling pathway can be modulated by cytokine treatment. Thus, Dectin-1 signaling reveals dynamic macrophage heterogeneity in inflammatory activation potential. ..
- Esteban A, Popp M, Vyas V, Strijbis K, Ploegh H, Fink G. Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages. Proc Natl Acad Sci U S A. 2011;108:14270-5 pubmed publisher..When macrophages expressing dectin-1 are exposed to Candida albicans mutants with increased exposure of ?-glucan, the loss of galectin-3 dramatically accentuates the failure to trigger an appropriate TNF-? response. ..
- Suram S, Brown G, Ghosh M, Gordon S, Loper R, Taylor P, et al. Regulation of cytosolic phospholipase A2 activation and cyclooxygenase 2 expression in macrophages by the beta-glucan receptor. J Biol Chem. 2006;281:5506-14 pubmed
- Taylor P, Brown G, Reid D, Willment J, Martinez Pomares L, Gordon S, et al. The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J Immunol. 2002;169:3876-82 pubmed..These observations imply the existence of an additional mannan-dependent receptor involved in the recognition of zymosan by resident peritoneal Mphi. ..
- Goodridge H, Shimada T, Wolf A, Hsu Y, Becker C, Lin X, et al. Differential use of CARD9 by dectin-1 in macrophages and dendritic cells. J Immunol. 2009;182:1146-54 pubmed..In such cells, Dectin-1, CARD9, and Bcl10 levels are not limiting, and data indicate that these cells express additional factors that restrict Dectin-1-CARD9 signaling for TNF-alpha induction. ..
- Rivera A, Hohl T, Collins N, Leiner I, Gallegos A, Saijo S, et al. Dectin-1 diversifies Aspergillus fumigatus-specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation. J Exp Med. 2011;208:369-81 pubmed publisher..fumigatus-specific CD4 T cells and enabling Th17 differentiation. ..
- Saijo S, Ikeda S, Yamabe K, Kakuta S, Ishigame H, Akitsu A, et al. Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity. 2010;32:681-91 pubmed publisher..Because IL-17A-deficient mice were highly susceptible to systemic candida infection, this study suggests that Dectin-2 is important in host defense against C. albicans by inducing Th17 cell differentiation. ..
- Rosas M, Liddiard K, Kimberg M, Faro Trindade I, McDonald J, Williams D, et al. The induction of inflammation by dectin-1 in vivo is dependent on myeloid cell programming and the progression of phagocytosis. J Immunol. 2008;181:3549-57 pubmed..This has implications for the mechanism by which myeloid cells are activated during fungal infections and the processes involved in the therapeutic manipulation of the immune system via exogenous dectin-1 stimulation or blockade. ..
- Rothfuchs A, Bafica A, Feng C, Egen J, Williams D, Brown G, et al. Dectin-1 interaction with Mycobacterium tuberculosis leads to enhanced IL-12p40 production by splenic dendritic cells. J Immunol. 2007;179:3463-71 pubmed..tuberculosis-induced IL-12p40 production by DC in which the receptor augments bacterial-host cell interaction and enhances the subsequent cytokine response through an unknown mechanism involving Syk signaling. ..
- Hermanz Falcón P, Arce I, Roda Navarro P, Fernández Ruiz E. Cloning of human DECTIN-1, a novel C-type lectin-like receptor gene expressed on dendritic cells. Immunogenetics. 2001;53:288-95 pubmedWe identified a new Ca2+-dependent lectin-like receptor gene, DECTIN-1 (HGMW-approved symbol CLECSF12), the human orthologue of mouse Dectin-1, coding for a putative type II transmembrane glycoprotein with an extracellular C-type lectin-..
- Gersuk G, Underhill D, Zhu L, Marr K. Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states. J Immunol. 2006;176:3717-24 pubmed..These data demonstrate one mechanism by which the pulmonary inflammatory response is tailored toward metabolically active cells, thereby avoiding unnecessary tissue damage with frequent inhalation of ubiquitous spores. ..
- Werner J, Metz A, Horn D, Schoeb T, Hewitt M, Schwiebert L, et al. Requisite role for the dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus. J Immunol. 2009;182:4938-46 pubmed publisher..fumigatus challenge was Dectin-1 dependent, and that neutralization of IL-17 significantly impaired A. fumigatus clearance. Collectively, these results support a requisite role for Dectin-1 in in vivo defense against A. fumigatus. ..
- Leal S, Cowden S, Hsia Y, Ghannoum M, Momany M, Pearlman E. Distinct roles for Dectin-1 and TLR4 in the pathogenesis of Aspergillus fumigatus keratitis. PLoS Pathog. 2010;6:e1000976 pubmed publisher..In contrast to Dectin 1(-/-) mice, cellular infiltration into infected TLR2(-/-), TLR4(-/-), and MD-2(-/-) mice corneas was unimpaired, ..
- Yokota K, Takashima A, Bergstresser P, Ariizumi K. Identification of a human homologue of the dendritic cell-associated C-type lectin-1, dectin-1. Gene. 2001;272:51-60 pubmed..Our results indicate that human DECTIN-1 shares many features with mouse dectin-1, including the generation of neck domain-lacking isoforms, which may down-regulate the co-stimulatory function of dectin-1. ..
- del Pilar Jiménez A M, Viriyakosol S, Walls L, Datta S, Kirkland T, Heinsbroek S, et al. Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a). Genes Immun. 2008;9:338-48 pubmed publisher..These results suggest that alternative splicing of the Dectin-1 gene contributes to susceptibility of C57BL/6 mice to coccidioidomycosis, and affects the cytokine responses of macrophages and mDCs to spherules...
- Gantner B, Simmons R, Underhill D. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J. 2005;24:1277-86 pubmed..The data demonstrate a mechanism by which C. albicans shape alone directly contributes to the method by which phagocytes recognize the fungus. ..
- Iliev I, Funari V, Taylor K, Nguyen Q, Reyes C, Strom S, et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science. 2012;336:1314-7 pubmed publisher..In humans, we identified a polymorphism in the gene for Dectin-1 (CLEC7A) that is strongly linked to a severe form of ulcerative colitis...
- Dennehy K, Ferwerda G, Faro Trindade I, Pyz E, Willment J, Taylor P, et al. Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors. Eur J Immunol. 2008;38:500-6 pubmed publisher..These findings establish the first example of Syk- and MyD88-coupled PRR collaboration, further supporting the concept that paired receptors collaborate to control infectious agents. ..
- del Fresno C, Soulat D, Roth S, Blazek K, Udalova I, Sancho D, et al. Interferon-? production via Dectin-1-Syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans. Immunity. 2013;38:1176-86 pubmed publisher..albicans-infected mice with Syk-deficient DCs. These data indicate that Dectin-induced IFN-? production by renal DCs is crucial for defense against C. albicans infection. ..
- Werner J, Gessner M, Lilly L, Nelson M, Metz A, Horn D, et al. Neutrophils produce interleukin 17A (IL-17A) in a dectin-1- and IL-23-dependent manner during invasive fungal infection. Infect Immun. 2011;79:3966-77 pubmed publisher..In summary, Dectin-1-dependent IL-17A production in the lungs during invasive fungal infection is mediated in part by CD11b(+) Ly-6G(+) neutrophils in an IL-23-dependent manner. ..
- Yadav M, Schorey J. The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood. 2006;108:3168-75 pubmed..These are the first results to establish a significant role for dectin-1, in cooperation with TLR2, to activate a macrophage's proinflammatory response to a mycobacterial infection. ..
- Taylor P, Tsoni S, Willment J, Dennehy K, Rosas M, Findon H, et al. Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat Immunol. 2007;8:31-8 pubmed
- Brown G, Gordon S. Immune recognition. A new receptor for beta-glucans. Nature. 2001;413:36-7 pubmed..1), there is evidence that another beta-glucan receptor is present on macrophages. Here we identify this unknown receptor as dectin-1 (ref. 2), a finding that provides new insights into the innate immune recognition of beta-glucans. ..
- Brown G, Taylor P, Reid D, Willment J, Williams D, Martinez Pomares L, et al. Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med. 2002;196:407-12 pubmed..Furthermore, these results identify Dectin-1 as a new target for examining the immunomodulatory properties of beta-glucans for therapeutic drug design. ..
- Qi C, Cai Y, Gunn L, Ding C, Li B, Kloecker G, et al. Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived ?-glucans. Blood. 2011;117:6825-36 pubmed publisher..These findings reveal the importance of different preparations of ?-glucans in the adjuvant therapy and allow for the rational design of immunotherapeutic protocols usable in clinical trials. ..
- Mora Montes H, Netea M, Ferwerda G, Lenardon M, Brown G, Mistry A, et al. Recognition and blocking of innate immunity cells by Candida albicans chitin. Infect Immun. 2011;79:1961-70 pubmed publisher..albicans cells but not with live cells. Therefore, chitin is normally not exposed to cells of the innate immune system but is capable of influencing immune recognition by blocking dectin-1-mediated engagement with fungal cell walls. ..
- Zhong J, Huang W, Deng Q, Wu M, Jiang H, Lin X, et al. Inhibition of TREM-1 and Dectin-1 Alleviates the Severity of Fungal Keratitis by Modulating Innate Immune Responses. PLoS ONE. 2016;11:e0150114 pubmed publisher..Inhibition of TREM-1 and Dectin-1 can alleviate the severity of corneal damage by downregulating the excessive inflammatory response. ..
- Agustinho D, de Oliveira M, Tavares A, Derengowski L, Stolz V, Guilhelmelli F, et al. Dectin-1 is required for miR155 upregulation in murine macrophages in response to Candida albicans. Virulence. 2017;8:41-52 pubmed publisher..Our results suggest that PRR-mediating signaling events are key drivers of miRNA-mediated gene regulation during fungal pathogenesis. ..
- Nanjappa S, Heninger E, WÃ¼thrich M, Gasper D, Klein B. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells. PLoS Pathog. 2012;8:e1002771 pubmed publisher..Our work has implications for designing vaccines against fungal infections in immune suppressed patients. ..
- Walsh N, Wuthrich M, Wang H, Klein B, Hull C. Characterization of C-type lectins reveals an unexpectedly limited interaction between Cryptococcus neoformans spores and Dectin-1. PLoS ONE. 2017;12:e0173866 pubmed publisher..neoformans spores and highlight challenges in using soluble receptor/ligand blocking experiments to recapitulate biologically relevant interactions. ..
- Yoshikawa F, Yabe R, Iwakura Y, de Almeida S, Saijo S. Dectin-1 and Dectin-2 promote control of the fungal pathogen Trichophyton rubrum independently of IL-17 and adaptive immunity in experimental deep dermatophytosis. Innate Immun. 2016;22:316-24 pubmed publisher..rubrum infection, impairing its resolution. Strikingly, neither adaptive immunity nor IL-17 response were required for fungal clearance, highlighting innate immunity as the main checkpoint in the pathogenesis of T. rubrum infection. ..
- Lefevre L, Lugo Villarino G, Meunier E, Valentin A, Olagnier D, Authier H, et al. The C-type lectin receptors dectin-1, MR, and SIGNR3 contribute both positively and negatively to the macrophage response to Leishmania infantum. Immunity. 2013;38:1038-49 pubmed publisher..These pathways also operated during infection of primary human macrophages. Therefore, our study promotes CLRs as potential targets for treatment, diagnosis, and prevention of visceral leishmaniasis. ..
- Ito T, Hirose K, Norimoto A, Tamachi T, Yokota M, Saku A, et al. Dectin-1 Plays an Important Role in House Dust Mite-Induced Allergic Airway Inflammation through the Activation of CD11b+ Dendritic Cells. J Immunol. 2017;198:61-70 pubmed..Dectin-1 (gene symbol Clec7a), a C-type lectin receptor, recognizes the fungal cell wall component ?-glucan, as well as some component(s) in ..
- Eberle M, Dalpke A. Dectin-1 stimulation induces suppressor of cytokine signaling 1, thereby modulating TLR signaling and T cell responses. J Immunol. 2012;188:5644-54 pubmed publisher..Our results show that SOCS1 is expressed via a new, NF-?B-independent pathway in Dectin-1-triggered murine BMMs and influences TLR cross talk and T cell priming. ..
- Gersuk G, Razai L, Marr K. Methods of in vitro macrophage maturation confer variable inflammatory responses in association with altered expression of cell surface dectin-1. J Immunol Methods. 2008;329:157-66 pubmed
- Blanco MenÃ©ndez N, del Fresno C, Fernandes S, Calvo E, Conde Garrosa R, Kerr W, et al. SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen Species Production in Dendritic Cells in Response to Candida albicans. J Immunol. 2015;195:4466-4478 pubmed publisherDectin-1 (Clec7a) is a paradigmatic C-type lectin receptor that binds Syk through a hemITAM motif and couples sensing of pathogens such as fungi to induction of innate responses...
- Zhang C, Wang S, Liao C, Shao S, Lasbury M, Durant P, et al. Downregulation of PU.1 leads to decreased expression of Dectin-1 in alveolar macrophages during Pneumocystis pneumonia. Infect Immun. 2010;78:1058-65 pubmed publisher..Results of this study indicate that downregulation of PU.1 during Pneumocystis pneumonia leads to decreased expression of Dectin-1 in AMs...
- Lilly L, Gessner M, Dunaway C, Metz A, Schwiebert L, Weaver C, et al. The ?-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22. J Immunol. 2012;189:3653-60 pubmed..Collectively, these results indicate that the ?-glucan receptor Dectin-1 contributes to lung inflammation and immunopathology associated with persistent fungal exposure via the production of IL-22...
- Loyola W, Custódio L, Felipe I, Conchon Costa I, Carvalho P, Quirino G, et al. Artin M enhances TNF-? production and phagocytosis of Candida albicans mediated by dectin-1 and mannose receptors. Int Immunopharmacol. 2012;12:378-83 pubmed publisher..These results suggest that Artin M, but not jacalin present in jack extract significantly increased TNF-? production and the activity of mannose and dectin-1 receptors. ..
- Stoppelkamp S, Reid D, Yeoh J, Taylor J, McKenzie E, Brown G, et al. Murine pattern recognition receptor dectin-1 is essential in the development of experimental autoimmune uveoretinitis. Mol Immunol. 2015;67:398-406 pubmed publisher..Thus dectin-1 plays a critical role in the ability of complete Freund's adjuvant to induce EAU in mice. ..
- Karnam A, Holla S, Balaji K. Sonic hedgehog-responsive lipoxygenases and cyclooxygenase-2 modulate Dectin-1-induced inflammatory cytokines. Mol Immunol. 2015;68:280-9 pubmed publisher..Together, the current study establishes Dectin-1-arbitrated host mediators that direct the differential regulation of immune responses during fungal infections and thus are potential candidates of therapeutic intervention. ..
- Gorjestani S, Yu M, Tang B, Zhang D, Wang D, Lin X. Phospholipase C?2 (PLC?2) is key component in Dectin-2 signaling pathway, mediating anti-fungal innate immune responses. J Biol Chem. 2011;286:43651-9 pubmed publisher..albicans infection in vivo. Together, these findings demonstrate that PLC?2 plays a critical role in CLR-induced signaling pathways, governing antifungal innate immune responses. ..
- Yang Z, Marshall J. Zymosan treatment of mouse mast cells enhances dectin-1 expression and induces dectin-1-dependent reactive oxygen species (ROS) generation. Immunobiology. 2009;214:321-30 pubmed publisher..05) after 2 h zymosan activation. Therefore, intracellular ROS generation in murine mast cells in response to zymosan is dependent on dectin-1 receptors. ..
- Parti R, Loper R, Brown G, Gordon S, Taylor P, Bonventre J, et al. Cytosolic phospholipase a2 activation by Candida albicans in alveolar macrophages: role of dectin-1. Am J Respir Cell Mol Biol. 2010;42:415-23 pubmed publisher..The results demonstrate that dectin-1 mediates the acute activation of cPLA(2)alpha in GM-CSF-primed alveolar macrophages, but not in the more delayed phase of AA release and GM-CSF-dependent prostanoid production. ..